反应详情

温度

100 °C

A mixture of methyl 2-cyclobutyl-5-iodo-4-methylbenzoate (compound 89.3, 3.0 g, 9.1 mmol), Zn(CN)2 (2.3 g, 19.6 mmol) and Pd(PPh3)4 (0.55 g, 0.47 mmol) in DMF (50 mL) was degassed and the system was charged with argon. The mixture was heated at 100° C. overnight, then cooled to room temperature. The mixture was quenched with saturated aqueous FeSO4 (20 mL), then diluted with EtOAc (200 mL). The solids were removed by filtration through Celite® and the filtrate was partitioned between water and EtOAc. The organic layer was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1) to yield 2.0 g (96%) of the title compound. 1H NMR (400 MHz, Chloroform-d) δ 8.03 (s, 1H), 7.34 (s, 1H), 4.26-4.13 (m, 1H), 3.89 (s, 3H), 2.59 (s, 3H), 2.46-2.32 (m, 2H), 2.16-1.98 (m, 3H), 1.90-1.78 (m, 1H).

1. customwas degassed
2. additionthe system was charged with argon
3. temperaturecooled to room temperature
4. customThe mixture was quenched with saturated aqueous FeSO4 (20 mL)
5. additiondiluted with EtOAc (200 mL)
6. customThe solids were removed by filtration through Celite®
7. customthe filtrate was partitioned between water and EtOAc
8. washThe organic layer was washed with brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe residue was purified by silica gel column chromatography (hexanes:EtOAc 30:1 to 20:1)